Abstract: Objective: To study the biomechanical effects of margin design on tooth tissue and dental prostheses on mandibular first molar with significant loss after root canal treatment (RCT). Methods: 3D finite element models of the right mandibular first molar with significant loss of coronal structure was established. After RCT, the loss was restored by endocrown,with two kinds of margin design. The models were loaded and maximum principal stress (εMax) of each part was observed. Results: Stress concentration in tooth and prostheses was different in these two kinds of restoration. Stress in enamel and prostheses were tend to be affected by margin design. Under vertical loading, peak value of enamel εMax in butt-joint margin group was 42.88% lower than that of the 90° margin group, with stress concentrating on dentino-enamel junction and enamel surface near margin area. Under vertical loading, peak value of ceramic εMax in butt-joint margin group was 45.55% lower than that of the 90° margin group, with stress concentrating on retention cavity inside the pulp chamber and tooth surface near margin area. Under lingual-buccal loading, peak value of ceramic εMax in butt-joint margin group was 12.58% lower than that of the 90° margin group, with stress concentrating on the bottom of the pulp chamber and tooth surface near margin area. Conclusion: Endocrown with butt-joint margin design was helpful to protect enamel and improve stress distribution of the prostheses. And from the view of biomechanics, it was positive to insure long-term stability.